Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence

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dc.contributor.authorRao, Vasudeven_ZA
dc.contributor.authorNeogi, Ujjwalen_ZA
dc.contributor.authorTalboom, Joshuaen_ZA
dc.contributor.authorPadilla, Ligiaen_ZA
dc.contributor.authorRahman, Mustafizuren_ZA
dc.contributor.authorFritz-French, Carien_ZA
dc.contributor.authorGonzalez-Ramirez, Sandraen_ZA
dc.contributor.authorVerma, Anjalien_ZA
dc.contributor.authorWood, Charlesen_ZA
dc.contributor.authorRuprecht, Ruthen_ZA
dc.contributor.authorRanga, Udaykumaren_ZA
dc.contributor.authorAzim, Tasnimen_ZA
dc.contributor.authorJoska, Johnen_ZA
dc.contributor.authorEugenin, Eliseoen_ZA
dc.contributor.authorShet, Anitaen_ZA
dc.contributor.authorBen_ZA
dc.date.accessioned2015-11-27T09:34:24Z
dc.date.available2015-11-27T09:34:24Z
dc.date.issued2013en_ZA
dc.description.abstractBACKGROUND: HIV-1 Clade C (Subtype C; HIV-1C) is responsible for greater than 50% of infections worldwide. Unlike clade B HIV-1 (Subtype B; HIV-1B), which is known to cause HIV associated dementia (HAD) in approximately 15% to 30% of the infected individuals, HIV-1C has been linked with lower prevalence of HAD (0 to 6%) in India and Ethiopia. However, recent studies report a higher prevalence of HAD in South Africa, Zambia and Botswana, where HIV-1C infections predominate. Therefore, we examined whether Southern African HIV-1C is genetically distinct and investigated its neurovirulence. HIV-1 Tat protein is a viral determinant of neurocognitive dysfunction. Therefore, we focused our study on the variations seen in tat gene and its contribution to HIV associated neuropathogenesis. RESULTS: A phylogenetic analysis of tat sequences of Southern African (South Africa and Zambia) HIV isolates with those from the geographically distant Southeast Asian (India and Bangladesh) isolates revealed that Southern African tat sequences are distinct from Southeast Asian isolates. The proportion of HIV1C variants with an intact dicysteine motif in Tat protein (C30C31) was significantly higher in the Southern African countries compared to Southeast Asia and broadly paralleled the high incidence of HAD in these countries. Neuropathogenic potential of a Southern African HIV-1C isolate (from Zambia; HIV-1C1084i), a HIV-1C isolate (HIV-1IndieC1) from Southeast Asia and a HIV-1B isolate (HIV-1ADA) from the US were tested using in vitro assays to measure neurovirulence and a SCID mouse HIV encephalitis model to measure cognitive deficits. In vitro assays revealed that the Southern African isolate, HIV-1C1084i exhibited increased monocyte chemotaxis and greater neurotoxicity compared to Southeast Asian HIV-1C. In neurocognitive tests, SCID mice injected with MDM infected with Southern African HIV-1C1084i showed greater cognitive dysfunction similar to HIV-1B but much higher than those exposed to Southeast Asian HIV1C. CONCLUSIONS: We report here, for the first time, that HIV-1C from Southern African countries is genetically distinct from Southeast Asian HIV-1C and that it exhibits a high frequency of variants with dicysteine motif in a key neurotoxic HIV protein, Tat. Our results indicate that Tat dicysteine motif determines neurovirulence. If confirmed in population studies, it may be possible to predict neurocognitive outcomes of individuals infected with HIV-1C by genotyping Tat.en_ZA
dc.identifier.apacitationRao, V., Neogi, U., Talboom, J., Padilla, L., Rahman, M., Fritz-French, C., ... (2013). Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence. <i>Retrovirology</i>, http://hdl.handle.net/11427/15406en_ZA
dc.identifier.chicagocitationRao, Vasudev, Ujjwal Neogi, Joshua Talboom, Ligia Padilla, Mustafizur Rahman, Cari Fritz-French, Sandra Gonzalez-Ramirez, et al "Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence." <i>Retrovirology</i> (2013) http://hdl.handle.net/11427/15406en_ZA
dc.identifier.citationRao, V. R., Neogi, U., Talboom, J. S., Padilla, L., Rahman, M., Fritz-French, C., ... & Prasad, V. R. (2013). Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence. Retrovirology, 10(1), 61.en_ZA
dc.identifier.ris TY - Journal Article AU - Rao, Vasudev AU - Neogi, Ujjwal AU - Talboom, Joshua AU - Padilla, Ligia AU - Rahman, Mustafizur AU - Fritz-French, Cari AU - Gonzalez-Ramirez, Sandra AU - Verma, Anjali AU - Wood, Charles AU - Ruprecht, Ruth AU - Ranga, Udaykumar AU - Azim, Tasnim AU - Joska, John AU - Eugenin, Eliseo AU - Shet, Anita AU - B AB - BACKGROUND: HIV-1 Clade C (Subtype C; HIV-1C) is responsible for greater than 50% of infections worldwide. Unlike clade B HIV-1 (Subtype B; HIV-1B), which is known to cause HIV associated dementia (HAD) in approximately 15% to 30% of the infected individuals, HIV-1C has been linked with lower prevalence of HAD (0 to 6%) in India and Ethiopia. However, recent studies report a higher prevalence of HAD in South Africa, Zambia and Botswana, where HIV-1C infections predominate. Therefore, we examined whether Southern African HIV-1C is genetically distinct and investigated its neurovirulence. HIV-1 Tat protein is a viral determinant of neurocognitive dysfunction. Therefore, we focused our study on the variations seen in tat gene and its contribution to HIV associated neuropathogenesis. RESULTS: A phylogenetic analysis of tat sequences of Southern African (South Africa and Zambia) HIV isolates with those from the geographically distant Southeast Asian (India and Bangladesh) isolates revealed that Southern African tat sequences are distinct from Southeast Asian isolates. The proportion of HIV1C variants with an intact dicysteine motif in Tat protein (C30C31) was significantly higher in the Southern African countries compared to Southeast Asia and broadly paralleled the high incidence of HAD in these countries. Neuropathogenic potential of a Southern African HIV-1C isolate (from Zambia; HIV-1C1084i), a HIV-1C isolate (HIV-1IndieC1) from Southeast Asia and a HIV-1B isolate (HIV-1ADA) from the US were tested using in vitro assays to measure neurovirulence and a SCID mouse HIV encephalitis model to measure cognitive deficits. In vitro assays revealed that the Southern African isolate, HIV-1C1084i exhibited increased monocyte chemotaxis and greater neurotoxicity compared to Southeast Asian HIV-1C. In neurocognitive tests, SCID mice injected with MDM infected with Southern African HIV-1C1084i showed greater cognitive dysfunction similar to HIV-1B but much higher than those exposed to Southeast Asian HIV1C. CONCLUSIONS: We report here, for the first time, that HIV-1C from Southern African countries is genetically distinct from Southeast Asian HIV-1C and that it exhibits a high frequency of variants with dicysteine motif in a key neurotoxic HIV protein, Tat. Our results indicate that Tat dicysteine motif determines neurovirulence. If confirmed in population studies, it may be possible to predict neurocognitive outcomes of individuals infected with HIV-1C by genotyping Tat. DA - 2013 DB - OpenUCT DO - 10.1186/1742-4690-10-61 DP - University of Cape Town J1 - Retrovirology LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence TI - Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence UR - http://hdl.handle.net/11427/15406 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15406
dc.identifier.urihttp://dx.doi.org/10.1186/1742-4690-10-61
dc.identifier.vancouvercitationRao V, Neogi U, Talboom J, Padilla L, Rahman M, Fritz-French C, et al. Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence. Retrovirology. 2013; http://hdl.handle.net/11427/15406.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDepartment of Psychiatry and Mental Healthen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2013 Rao et al.; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceRetrovirologyen_ZA
dc.source.urihttp://www.retrovirology.com/en_ZA
dc.subject.otherClade C HIV-1en_ZA
dc.subject.otherSubtype C HIV-1en_ZA
dc.subject.otherHIV-1 Taten_ZA
dc.subject.otherTat dicysteineen_ZA
dc.subject.otherNeuropathogenesisen_ZA
dc.subject.otherSCID-HIVE mouse modelen_ZA
dc.subject.otherHIV-1 Tat C31S polymorphismen_ZA
dc.subject.otherNeuroaidsen_ZA
dc.subject.otherHIV dementiaen_ZA
dc.titleClade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulenceen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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